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drug action iv > Hepatitis (MC) - Block 3 > Flashcards

Hepatitis (MC) - Block 3 Flashcards

1
Q

What the types of HAV vaccines? Components?

A

Havrix and Vaqata: both contain inactivated virus

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2
Q

What are types of HBV vaccines? Components?

A

Engerix, Recombivax HB: Envelope proteins and HBsAg

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2
Q

What are the functions of IFN therapy?

A

Interfere with viral replication within host cell:
* Triggers host defence
* Induction of apoptosis in infected cells

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3
Q

What is pegylation?

A

Covalent modification of polyethylene glycol chains

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4
Q

Types of pegylated interferon?

A

IFN-a-2b: Pegintron
IFN-a-2a: Pegasys

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5
Q

How do IFN come in pegylated formulations?

A
  1. Reduces immunogenicity by masking agent from host immune system
  2. Protection from proteolytic degradation
  3. Increases solubility of hydrophobic molecules
  4. Increases hydrodynamic size -> prolonging circulation time and preventing renal clearance
  5. Improves PK -> QW instead of 3 weekly injections
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6
Q
A
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6
Q

ADR of pegylated IFN? CI?

A
  1. Flu
  2. Depression
  3. SZ

CI: renal insufficiency

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7
Q

What is polymerases?

A

Catalyze the polymerization during transcription replication process
* HBV has reverse transcriptase

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8
Q

Examples of Polymerase inhibitor?

A

Lamivudine (Epivir)

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9
Q

MOA of lamivudine?

A

L-confirmation HBV polymerase (reverse transcriptase) inhibitor:
* Prodrug must be phosphorylated (triphosphate) to become active
* Competes with deoxycytidine triphosphate for incorporation into viral DNA
* Competitive inhibitor of HBV polymerase for chain termination

Resistance emerges rapidly

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10
Q

MOA of adefovir dipivoxil?

A

Guanine analogue (prodrug):
* Acyclic nucleoside

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11
Q

Advantages of adefovir over lamivudine?

A

Resistance is slower to develop

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11
Q

MOA of entecavir?

A

Carbocyclic analogue of guanine that selectively inhibits HBV:
* Methylene group that bind to methionine on active site

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12
Q

Structure of Telbivudine?

A

L-isomer of thymidine: more effective than Lamivudine or Adefovir

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13
Q

What is the produg and salt form of tenofovir?

A

Prodrug: Tenofovir Disoproxil
Salt: Tenofovir Disoproxil Fumarate (TDF)

14
Q

What is the BBW for anti-HBV therapies

A

Abrupt DC can cause acute exacerbations of HBV dx and hepatic dysfunction

15
Q

What are the tx for HBV?

A

Pegylated IFN: Pefintron and Pegasys
Polymerase Inhibitor: Lamivudine, Adefovir, Entecavir, Telbivudine, Tenofovir

16
Q

Tx for Hep C?

A
  1. Pegintron, Pegasys, non-peg IFN-a-2a and 2b
  2. Ribavirin
  3. Telaprevir
  4. Sofosbuvir
  5. Glecaprevir
  6. Ledipasvir
  7. Velpatasvir
  8. Pibrentasvir
17
Q

Structure of ribavirin?

A

Mimics guanosine (not an analogue because it isn’t an actual base)

18
Q

MOA of ribavirin?

A
  1. Inhibits of certain viral RNA-dependent RNA polymerase
  2. Inhibits cellular IMP dehydrogenase (IMP)
19
Q

Due to ribavirin’s broad activity, what is a possible ADR associated with the drug?

A

Teratogenicity

20
Q

MOA of Telaprevir? Indications?

A

Protease (serine) inhibitors
* Diketo group acts as a trap for serine at the active site (transition state) on the protease

Indication: approved against genotype 1 of HCV

21
Q

Describe the activity of Ribavirin?

A

Broad activity against DNA and RNA viruses

22
Q

MOA of sofosbuvir?

A

Targets NS5B-RNA polymerase prodrug
* Carrier linked bioprecursor
* False substrate for RNA polymerase

23
Q

Indication for sofosbuvir?

A
  1. Combo with ribavirin for HCV 2-3
  2. Curative in some cases
24
Q

What are your NS5A inhibitors?

A

Ledipasvir
Velpatasvir
Pibrentasvir

25
Q

What is the MOA of NS5A inhibitors?

A

Zinc binding enzyme at allosteric site

26
Q

How is sofosbuvir metabolized?

A

To uridine triphosphate mimic -> incorporated into RNA by NS5B polymerase

27
Q

Ledipasvir/Sofosbuvir

A

Harvoni

28
Q

Velpatasvir/Sofosbuvir

A

Epclusa

29
Q

Pibrentasvir/Glecaprevir

A

Mavyret

30
Q

MOA of glecaprevir?

A

NS3/4A protease inhibitor -> new viral particles can’t fully develop/mature
* Does not trap
* Cyclic peptide mimic

drug action iv (28 decks)

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